Agrawal A K, Pampori N A, Shapiro B H
Laboratories of Biochemistry, University of Pennsylvania, School of Veterinary Medicine, Philadelphia 19104-6048.
Toxicol Appl Pharmacol. 1991 Mar 15;108(1):96-106. doi: 10.1016/0041-008x(91)90272-g.
Rats, neonatally treated with monosodium aspartate (MSA), exhibited developmental defects through adulthood that were characterized by stunted growth, obesity, and reduced size of the liver, kidney, adrenals, and pituitary. Adult male and female rats treated with 4 mg of MSA had no detectable plasma growth hormone as determined from serial blood samples taken every 15 min for 8 consecutive hr. Associated with this loss of circulating growth hormone in the males was a dramatic decline in in vivo and in vitro hexobarbital metabolism and hepatic cytochrome P450 to female levels. The loss of plasma growth hormone in the females had no effect on the already low levels of hepatic monooxygenases. At 2 mg/g body weight, MSA produced both sex- and dose-dependent effects that were far more subtle than the full-blown obesity and growth retardation associated with the larger 4-mg dose. While the mean concentration of circulating growth hormone was reduced 70 to 90% in 2-mg-MSA-treated rats, the sexually dimorphic, ultradian patterns of growth hormone secretion were undisturbed. Affected males continued to secrete a pulse of growth hormone every 3 hr, albeit at greatly reduced amplitudes, interposed by normally undetectable baselines. Similarly, 2-mg-MSA-treated females had greatly reduced mean levels of plasma growth hormone, but with the usual secretion of multiple pulses never dropping to baseline. Surprisingly, the sex-dependent, hepatic monooxygenases, which are normally regulated by the ultradian secretions of growth hormone, were unaffected by the 2-mg MSA treatment. Our results suggest that while an ultradian pulse of circulating growth hormone is necessary for the characteristically male profile of hepatic monooxygenases, neither the amplitude of the secretory peaks nor their total growth hormone content is critical.
新生期用天冬氨酸单钠（MSA）处理的大鼠，在成年期表现出发育缺陷，其特征为生长发育迟缓、肥胖，肝脏、肾脏、肾上腺和垂体体积减小。用4毫克MSA处理的成年雄性和雌性大鼠，在连续8小时每15分钟采集一次的系列血样中，未检测到血浆生长激素。雄性大鼠循环生长激素的这种丧失与体内和体外己巴比妥代谢以及肝细胞色素P450降至雌性水平的显著下降有关。雌性大鼠血浆生长激素的丧失对已经很低的肝脏单加氧酶水平没有影响。以2毫克/克体重的剂量，MSA产生了性别和剂量依赖性效应，这些效应比与较大的4毫克剂量相关的全面肥胖和生长迟缓要微妙得多。虽然在接受2毫克MSA处理的大鼠中，循环生长激素的平均浓度降低了70%至90%，但生长激素分泌的性二态性超日节律模式未受干扰。受影响的雄性大鼠每3小时仍会分泌一次生长激素脉冲，尽管幅度大大降低，其间是通常无法检测到的基线。同样，接受2毫克MSA处理的雌性大鼠血浆生长激素的平均水平大大降低，但仍会正常分泌多个脉冲，且从未降至基线水平。令人惊讶的是，通常由生长激素的超日分泌调节的性别依赖性肝脏单加氧酶，不受2毫克MSA处理的影响。我们的结果表明，虽然循环生长激素的超日脉冲对于肝脏单加氧酶典型的雄性特征是必要的，但分泌峰的幅度及其生长激素总量都不是关键因素。
